Natural killer cell cytotoxicity receptor 3 ligand 1 (NCR3LG1) (NCR3LG1)

Natural killer cell cytotoxicity receptor 3 ligand 1, commonly known as B7-H6, is a type I transmembrane protein belonging to the B7 family of immune-modulating molecules [1, 2]. It serves as a specific ligand for NKp30 (NCR3), a potent activating receptor expressed on natural killer (NK) cells [2]. Under physiological conditions, B7-H6 is not detected in healthy tissues, but it is highly upregulated on the surface of various tumor cells, including those in leukemia, lymphoma, and several solid cancers [3]. The binding of B7-H6 to NKp30 triggers NK cell activation, leading to the secretion of pro-inflammatory cytokines like IFN-gamma and the direct lysis of the target cell [2, 4]. However, tumors can employ immune evasion strategies by shedding the extracellular domain of B7-H6, creating a soluble form (sB7-H6) that acts as a decoy to block NKp30 and downregulate NK cell activity [4]. Due to its tumor-specific expression profile, B7-H6 is an attractive target for immunotherapy, with various modalities such as bispecific antibodies and CAR-T cells currently under investigation to enhance anti-tumor immunity [3, 5]. Sources: [1] UniProt Consortium. UniProtKB - Q682Q4 (NCR3L_HUMAN). [2] Brandt CS, et al. The B7 family member B7-H6 is a tumor cell ligand for the NK cell activating receptor NKp30. J Exp Med. 2009;206(7):1495-1503. [3] Cao G, et al. B7-H6: A novel target for cancer immunotherapy. Front Immunol. 2020;11:593335. [4] Schlecker E, et al. Tumor-derived soluble B7-H6 leads to NK cell dysfunction. Cancer Res. 2014;74(11):2988-3000. [5] Wu MR, et al. A NKp30-based chimeric antigen receptor (CAR) redirects T cells to B7-H6-positive solid tumors. Mol Ther. 2015;23(12):1865-1875.

Other names

B7-H6B7H6NCR3LG1DKFZp686O24166

B7-H6 targeted therapies primarily function by redirecting cytotoxic effector cells, such as T cells or NK cells, to B7-H6-expressing tumor cells. This is achieved through bispecific antibodies that bridge B7-H6 on the tumor with activating receptors (like CD3 or CD16) on the immune cells, or through CAR-T cells engineered to recognize B7-H6, thereby triggering direct lysis of the malignancy [3, 5].